U.S. Pat. No. 5,532,241 (hereinafter referred to as the '241 patent) discloses a variety of piperidine and piperazine derivatives and their pharmaceutically acceptable salts, processes for their preparation, pharmaceutical compositions comprising the derivatives, and methods of use thereof. These compounds are active on the central nervous system, especially in terms of 5-HT1A-agonist and 5-HT-reuptake inhibition. They are furthermore active as serotonin agonists and antagonists. These compounds and their physiologically acceptable acid addition salts can, therefore, be used as active ingredients for anxiolytics, antidepressants, antipsychotics, neuroleptics, and antihypertensives. Among them, Vilazodone hydrochloride, 5-[4-[4-(5-Cyanoindol-3-yl)butyl]piperazin-1-yl]benzofuran-2-carboxamide hydrochloride, is a serotonergic antidepressant that is used for the treatment of major depressive disorder (MDD). Vilazodone hydrochloride is represented by the following structural formula:

Vilazodone was approved by the FDA for use in the United States to treat major depressive disorder and it is sold under the trade name VIIBRYD™. It is orally administered as tablets containing 10 mg, 20 mg and 40 mg of vilazodone as the hydrochloride salt.
PCT Publication No. WO02/102794A2 (hereinafter referred to as the '794 publication) discloses several crystalline modifications (Crystalline Forms I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XIII, XIV, XV and XVI) of vilazodone hydrochloride, which include six anhydrate forms, three hydrated fowls and six solvated forms, wherein Form I is an acetone solvate; Forms II, XV and X are tetrahydrofuran solvates; Form XI is a methanol solvate; and Form XIV is an n-heptane solvate. Form V is monohydrate, Form VI is a sesquihydrate and Form VIII is a hemihydrate. Forms III, IV, VII and IX are anhydrate crystalline forms of vilazodone hydrochloride. Form XIII is a crystalline modification of vilazodone dihydrochloride. These crystalline modifications are characterized by powder X-ray diffraction (P-XRD), Infra Red spectroscopy (IR), RAMAN spectroscopy and thermal analysis.
The '794 publication teaches that the product (Vilazodone hydrochloride) obtained according to the process described in the prior art, for example, as per the process exemplified in example 4 of U.S. Pat. No. 5,532,241, followed by customary work-up to produce vilazodone free base and subsequent precipitation of vilazodone hydrochloride by treating the solution of the vilazodone base (700 mg) in 2-propanol (30 ml) with 2-propanolic HCl-solution (Merck-Art. No. 1.00326), is a mixture of amorphous vilazodone hydrochloride and crystallized vilazodone hydrochloride and the vilazodone free base.
A similar process for the precipitation of vilazodone hydrochloride is also reported in Journal of Medicinal Chemistry, 2004, Vol. 47, No. 19, pages 4684-4692 (hereinafter referred to as the ‘JMC article’). As per the process reported in the JMC article (see column-1, lines 47-57 of Page No. 4690), the vilazodone hydrochloride is precipitated by dissolving vilazodone free base (0.7 g) in 30 ml of hot 2-propanol to form a solution, followed by slow addition of HCl-saturated 2-propanol at room temperature until complete precipitation occurred to yield 0.6 g of vilazodone hydrochloride (Melting Point: 277-279° C.).
The '794 publication further teaches that there is no clear teaching elsewhere in the '241 patent of any alternative route or modification to the process which would generate new crystal modifications of vilazodone hydrochloride or new solvates or hydrates of vilazodone hydrochloride in different crystal modifications.
The '794 publication further teaches an amorphous form of vilazodone hydrochloride. While the '794 publication mentions that a pure amorphous form of vilazodone hydrochloride has been found, there is no clear disclosure about amorphous form since the '794 publication neither disclosed the characterization data (X-ray diffractogram) nor described the process for the preparation of a pure amorphous form of vilazodone hydrochloride.
The processes described in the aforementioned prior art have failed to produce a pure amorphous form of vilazodone hydrochloride substantially free of crystalline forms. Instead, the prior art processes yield a solid state form containing the mixture of amorphous vilazodone hydrochloride and crystallized vilazodone hydrochloride and the vilazodone free base, which is not suitable for pharmaceutical use.
Polymorphism is the ability of a solid material to exist in more than one form or crystal structure. Amorphous solids consist of disordered arrangement of molecules and do not possess a distinguishable crystal lattice. The amorphous form is generally more soluble than the crystalline form and thus contributes more in the bioavailability.
An important solid state property of a pharmaceutical compound is its rate of dissolution in aqueous fluid. The rate of dissolution of an active ingredient in a patient's stomach fluid may have therapeutic consequences since it imposes an upper limit on the rate at which an orally-administered pharmaceutical compound may reach the patient's bloodstream. The rate of dissolution is a consideration in formulating syrups, elixirs and other liquid medicaments. The solid state form of a compound may also affect its behavior on compaction and its storage stability.
It has been disclosed in the art that the amorphous forms of a number of pharmaceutical compounds exhibit superior dissolution characteristics and in some cases different bioavailability patterns compared to crystalline forms [Konno T., Chem. Pharm. Bull., 38, 2003 (1990)]. For some therapeutic indications, one bioavailability pattern may be favored over another.
Solvent medium and mode of isolation play very important roles in obtaining one polymorphic form over another.
Amorphous form of vilazodone hydrochloride substantially free of crystalline forms has not been prepared, isolated, or characterized in the literature.
Hence, there is a need in the art for highly pure and stable amorphous form of vilazodone hydrochloride essentially free of crystalline forms, a process for its preparation and a pharmaceutical composition thereof.